NKG2A Protein, Human (HEK293, His)

NKG2A Protein, an immune inhibitory receptor crucial for self-nonself discrimination, forms a complex with KLRD1 on cytotoxic and regulatory lymphocyte subsets, recognizing the non-classical major histocompatibility (MHC) class Ib molecule HLA-E loaded with self-peptides from the signal sequence of classical MHC class Ia molecules. This recognition allows cytotoxic cells to monitor MHC class I expression in healthy cells and promotes self-tolerance. Upon binding to HLA-E-peptide complexes, NKG2A transmits intracellular signals through two immunoreceptor tyrosine-based inhibition motifs (ITIMs), recruiting INPP5D/SHP-1 and INPPL1/SHP-2 tyrosine phosphatases to oppose signals from activating receptors. As a key inhibitory receptor on natural killer (NK) cells, NKG2A regulates their activation and effector functions, countering T cell receptor signaling on a subset of memory/effector CD8-positive T cells and distinguishing harmless from pathogenic antigens. In the HLA-E-rich tumor microenvironment, NKG2A acts as an immune inhibitory checkpoint, contributing to the progressive loss of effector functions in NK cells and tumor-specific T cells, a phenomenon known as cell exhaustion. Notably, during viral infection, NKG2A recognizes HLA-E in complex with human cytomegalovirus-derived peptides, inhibiting NK cell cytotoxicity and facilitating viral immune escape.